Effects of bisphenol A and its alternative bisphenol F on Notch signaling and intestinal development: A novel signaling by which bisphenols disrupt vertebrate development. (August 2020)

• Record Type: Journal Article
• Authors: Zhu, Min; Li, Yuanyuan; Niu, Yue; Li, Jinbo; Qin, Zhanfen
• Is Part Of: Environmental pollution. Volume 263(2020)Supplement Part B
• Publication Date: 2020-08
• Subjects: Bisphenol analogues -- Notch signaling -- Xenopus laevis -- Intestinal development; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2020.114443
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: We previously found bisphenol A (BPA) alternative, bisphenol F (BPF) upregulated Notch-related gene expression in intestines of the African clawed frog Xenopus laevis, suggesting an agonistic action on Notch signaling, a crucial signaling in multiple biological processes during development. Here, we aimed to confirm the actions of BPA and BPF on Notch signaling and to reveal their effects on intestinal development. Using X. laevis, an excellent model for developmental biology, we found that 10–1000 nM BPA and BPF significantly elevated Notch-related gene expression in a concentration-dependent manner. Subsequently, exceptional cell proliferation as well as intestinal histological changes were observed in treated intestines. Importantly, Notch inhibitor markedly suppressed the effects of BPA and BPF described above. Furthermore, we employed rat intestinal epithelium cells (IEC-6), an ideal in vitro model of intestinal epithelial cell differentiation, to confirm the effects of bisphenols. As expected, BPA and BPF upregulated Notch-related gene expression and induced the translocation of the Notch intracellular domain to the nucleus, followed by exceptional cell proliferation and differentiation, whereas Notch inhibitor antagonized the effects caused by BPA and BPF. All results strongly demonstrate that both BPA and BPF activate Notch signaling and subsequently disrupt intestinal development in vertebrates. Given its fundamental roles in multiple developmental processes, we propose that Notch signaling is an important and general target signaling of bisphenols in many developing tissues of vertebrates including humans. Graphical abstract: Image 1 Highlights: Nanomolar BPA and BPF activated Notch signaling in vivo and in vitro . BPA and BPF disrupted intestinal development in Xenopus laevis . Intestinal development alterations caused by bisphenols are via Notch signaling. Abstract : BPA and its alternative BPF activate Notch signaling and subsequently alter intestinal development in vertebrates.